Vaccine Generation of Protective Ebola Antibodies and Identification of Conserved B-Cell Signatures

The Journal of Infectious Diseases
Alberto CagigiNancy J Sullivan

Abstract

We recently identified a single potently neutralizing monoclonal antibody (mAb), mAb114, isolated from a human survivor of natural Zaire ebolavirus (EBOV) infection, which fully protects nonhuman primates (NHPs) against lethal EBOV challenge. To evaluate the ability of vaccination to generate mAbs such as mAb114, we cloned antibodies from NHPs vaccinated with vectors encoding the EBOV glycoprotein (GP). We identified 14 unique mAbs with potent binding to GP, 4 of which were neutralized and had the functional characteristics of mAb114. These vaccine-induced macaque mAbs share many sequence similarities with mAb114 and use the same mAb114 VH gene (ie, IGHV3-13) when classified using the macaque IMGT database. The antigen-specific VH-gene repertoire present after each immunization indicated that IGHV3-13 mAbs populate an EBOV-specific B-cell repertoire that appears to become more prominent with subsequent boosting. These findings will support structure-based vaccine design aimed at enhanced induction of antibodies such as mAb114.

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Citations

Mar 27, 2019·Obstetrics and Gynecology·Flor M Munoz, Denise J Jamieson
Jun 18, 2019·The Pediatric Infectious Disease Journal·Alastair Murray, Helen Y Chu
Oct 9, 2019·Nature Medicine·Stefanie A EhrhardtFlorian Klein
Feb 26, 2020·Nature Immunology·Susan K PierceNaomi Taylor
Dec 1, 2020·Frontiers in Immunology·Valentina AgnolonFrançois Spertini
Sep 19, 2020·Antiviral Research·Mao IsonoAyato Takada
Sep 30, 2021·International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases·Marie JaspardDenis Malvy

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